In the US, RNA polymerase read a synthetic eight-letter DNA alphabet
Scientists at the University of California San Diego in the United States showed that the RNA polymerase of the bacterium Escherichia coli can accurately read and transcribe a synthetic eight-letter genetic alphabet. All known life on Earth uses four DNA letters. ScienceDaily reports on the results.
How the enzyme recognizes artificial bases
RNA polymerase reads DNA and synthesizes RNA — this is the first stage of gene expression. The researchers combined biochemical experiments with high-resolution cryo-electron microscopy to track how the enzyme recognizes and incorporates two synthetic base pairs that do not exist in nature.
Structural images showed that RNA polymerase uses many of the same biochemical and structural signals to recognize artificial letters as it does for natural base pairs. This helps explain why the enzyme can copy information encoded in an expanded genetic alphabet.
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Two studies of the expanded code
The main work, titled Structural Basis of Transcription of the Hachimoji Eight-Letter Alphabet by E. coli RNA Polymerase, was published on September 2, 2026, in the journal Nature Communications. It was led by Dong Wang, a professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego.
In another study by the same team, published on August 12, 2026, in the Proceedings of the National Academy of Sciences, scientists found that RNA polymerase can also recognize another pair of synthetic bases without hydrogen bonds, which usually help hold DNA base pairs together.
A detailed study of the transcription of unnatural DNA letters could provide a foundation for creating expanded genetic systems. Possible applications include diagnostic tools, therapeutics, and engineered biological systems with functions not found in nature. Previously, expanded genetic alphabets were already used to create synthetic DNA molecules capable of recognizing liver cancer cells.
